The instant invention relates to novel amide and urea derivatives of .alpha.-aminoacids containing substituted imidazole or 1,2,4-triazole moieties which antagonize the binding of angiotensin II (AII) to cellular receptors. This AII antagonist property renders these compounds useful for treatment of angiotensin-related hypertension.
The enzyme renin acts on a blood plasma .alpha..sub.2 -globulin, angiotensinogen, to produce angiotensin I, which is then converted by angiotensin-converting enzyme to AII. The latter substance is a powerful vasopressor agent which has been implicated as a causative agent for producing high blood pressure in various mammals, such as rats, dogs, and humans. The compounds of this invention inhibit the action of AII at its receptors on target cells and thus prevent the increase in blood pressure produced by this hormone-receptor interaction. By administering a compound of the instant invention to a species of mammal with hypertension due to AII, the blood pressure is reduced. The compounds of the invention are also useful for the treatment of congestive heart failure, hyperaldosteronism and glaucoma.
European Application Number 253,310 discloses imidazoles of the formula ##STR1##
The compounds are disclosed as having utility in treating hypertension and congestive heart failure.
European Application Number 323,841 discloses substituted pyrrole-, pyrazole-, and triazole-containing compounds of the formulas ##STR2##
European Application Number 324,377 discloses a pharmaceutical composition of a diuretic or a nonsteroidal antiinflammatory drug useful for blocking the angiotensin II receptor.
U.S. Pat. No. 4,355,040 discloses imidazole-5-acetic acid derivatives of the formula ##STR3## wherein R.sup.1 is lower alkyl, cycloalkyl or, phenyl which may be substituted with one to three of halogen, nitro, amino, mono(lower alkyl)amino, di(lower alkyl)amino, lower alkyl, lower alkoxyl, benzyloxyl or/and hydroxyl; X.sup.1, X.sup.2 and X.sup.3 are each hydrogen, halogen, nitro, amino, lower alkyl, lower alkoxyl, benzyloxyl or hydroxyl; Y is halogen and R.sup.2 is hydrogen or lower alkyl; provided that X.sup.1 is halogen, lower alkyl, lower alkoxyl, benzyloxyl or hydroxyl when R.sup.1 is unsubstituted or substituted phenyl only with one halogen, di(lower alkyl)amino, lower alyl or lower alkoxyl, and its salts. The compounds are disclosed as having hypertensive activity.